TY - JOUR T1 - Yolk sac erythromyeloid progenitors sustain erythropoiesis throughout embryonic life JF - bioRxiv DO - 10.1101/2020.02.27.968230 SP - 2020.02.27.968230 AU - Francisca Soares-da-Silva AU - Odile Burlen-Defranoux AU - Ramy Elsaid AU - Lorea Iturri AU - Laina Freyer AU - Odile Sismeiro AU - Perpétua Pinto-do-Ó AU - Elisa Gomez-Perdiguero AU - Ana Cumano Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/03/01/2020.02.27.968230.abstract N2 - The first hematopoietic cells are produced in the yolk sac and are thought to be rapidly replaced by the progeny of hematopoietic stem cells. Here we document that hematopoietic stem cells do not contribute significantly to erythrocyte production up until birth. Lineage tracing of yolk sac-derived erythromyeloid progenitors, that also contribute to tissue resident macrophages, shows a progeny of highly proliferative erythroblasts, that after intra embryonic injection, rapidly differentiate. These progenitors, similar to hematopoietic stem cells, are c-Myb dependent and are developmentally restricted as they are not found in the bone marrow. We show that erythrocyte progenitors of yolk sac origin require lower concentrations of erythropoietin than their hematopoietic stem cell-derived counterparts for efficient erythrocyte production. Consequently, fetal liver hematopoietic stem cells fail to generate megakaryocyte and erythrocyte progenitors. We propose that large numbers of yolk sac-derived erythrocyte progenitors have a selective advantage and efficiently outcompete hematopoietic stem cell progeny in an environment with limited availability of erythropoietin. ER -